Arthritic disorders are the second leading cause of losses in time and earnings in the United States. Approximately nine percent (9%) of all arthritis sufferers are afflicted with a type of arthritis known as rheumatoid arthritis. Of these, approximately fifty-six percent (56%) ultimately will have involvement of the knee joint, eighty-seven percent (87%) of the hand joint and somewhat smaller percentages will have involvement of other joints such as the ankle, elbow and shoulder.
The source of disability for the sufferer of rheumatoid arthritis is an inflammatory response, of unknown origin, in the synovium, or lining, of the afflicted joint. This chronic inflammation, or synovitis, leads to pannus formation and, eventually, enzymatic destruction of the joint cartilage.
Presently, the primary method of treating rheumatoid arthritis is by use of compounds directed at blocking the inflammatory process. Unfortunately, these attempts are quite often unsuccessful. In such instances, the primary alternative is the surgical excision of the inflamed synovium in a procedure known as surgical synovectomy. While, in many cases, this procedure proves to temporarily arrest the disease, it also has a significant number of drawbacks and limitations. Among these are limitations on just how much of the inflamed synovium can be surgically excised; the operation itself; the risks and dangers inherent therein; and the required lengthy recovery period, much of which is spent in the hospital.
In order to overcome these problems, attempts (albeit unsuccessful) have been made with radiation synovectomy. The prior art reveals that intra-articular colloidial Gold-198 (.sup.198 Au) was reported to abate inflamed synovium (Fellinger, et al., 33 WEIN Z. INN, Med. 351, 1951). However, this procedure did not gain acceptance until the report of Ansell, et al., 22 Ann. Rheum. Dis. 435 (1963). Unfortunately, due to .sup.198 Au emission of a high energy photon (gamma emission) these attempts proved unsatisfactory. The presence of the aforementioned emission poses dangers to the patient by increasing the whole body dose, thereby exposing healthy tissue to the destructive radioactivity, and poses substantial difficulties with radiation protection for hospital personnel.
Other radionuclides have also been unsuccessfully utilized in radiation synovectomy. These include Erbium-169 (.sup.169 Er) Menkes, et al., 36 Ann. Rheum. Dis. 254 (1977); Rhenium-186 (.sup.186 Re) Deckart, et al., 3 Radiobiol, Radiother 363 (1979) and DelBarre et al., 2 Nouv. Presse. Med 1372 (1973); Phosphorus-32 (.sup.32 P) Wenston, et al., 14 J. Nuc. Med 886 (1973), and Yttrium-90 (.sup.90 Y) Gumpel, et al., 48 Br. J. Radiol. 377 (1975).
Disadvantages common to each of these radionuclides proved to be their long physical half-lives and the occurence of radioleakage in significant amounts, from the affected joints. (See also Oka, et al., 17 Acta Rheum. Scand. 148 (1971) and Virkkunen, et al., 13 Acta Rheum. Scand., 1967). There exists, however, notable exceptions to these isotopic characteristics.
Currently the preferred and only suitable radionuclide in the prior art is Dysprosium-165 (.sup.165 Dy) in ferric hydroxide. Sledge, et al., 182 Clin. Ortho, and Rel. Research 37 (1984) (hereinafter referred to as "Sledge"). Sledge has found that the use of .sup.165 Dy can overcome the problems previously encountered by use of the aforementioned radionuclides in radiation synovectomy. This is because .sup.165 Dy is a beta emitter, has a maximum soft tissue penetration of approximately 5.7 mm, forms a larger colloid which reduces the effects of leakage of the injection close to the lymph nodes, and has an extremely short half-life of 2.3 hours which further reduces the effects of potential leakage.
These are qualities which the prior art has reported to be desirable when selecting an appropriate isotope for radiation synovectomy (Sledge, et al., 20 Arthritis Rheum 1334 (1977), Noble, et al., 65A J. Bone Joint Surg. 381 (1983), and Deckert and Gumpel, both supra).
While .sup.165 Dy's short half-life is a major characteristic noted by Sledge in the prior art as making it a suitable candidate for radiation synovectomy, this short half-life also proves to be its major limitation. .sup.165 Dy requires a nuclear reactor to be produced. It also must be injected within a few hours of its manufacture to be effective. As a result, its utility in radiation synovectomy is severely limited by geographical and distribution factors.
Accordingly, there remains an obvious need for an effective radioactive compound that will have both utility in radiation synovectomy and will be able to be prepared in, and distributed from, a central location using existing transportation channels.